ABCB6 knockdown suppresses melanogenesis through the GSK3-β/β-catenin signaling axis in human melanoma and melanocyte cell lines

ABCB6 敲低通过人类黑色素瘤和黑色素细胞系中的 GSK3-β/β-catenin 信号轴抑制黑色素生成

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作者:Qiuyun She, Yingying Dong, Dong Li, Ran An, Ting Zhou, Xiaoqi Nie, Ronghua Pan, Yunhua Deng

Background

Melanogenesis is a multistep process in which melanocytes produce melanin pigments within melanosomes. However, the roles played by the biological factors and pathways in this process are not yet fully understood.

Conclusion

Our findings suggest that ABCB6 is a key regulator of melanogenesis via the GSK3-β/β-catenin signaling pathway. However, further in-depth studies are essential to uncover the relationship between ABCB6 and pigmentation disorders.

Methods

Real-time PCR and western blotting were used to assess the knockdown efficiency of ABCB6 in MNT-1 and PIG1 stable cell lines. Cleavage by NaOH was used to determine melanin content, while the number of melanosomes was examined for each stage by transmission electron microscopy. Immunofluorescence microscopy was used to evaluate endogenous protein location. Differentially expressed genes were detected using RNA sequencing, and gene expression was assessed by quantitative real-time PCR. KEGG mapping was used for pathway enrichment analysis. Co-immunoprecipitation was used for protein-protein interactions analysis.

Objective

To investigate the role of ATP-binding cassette subfamily B member 6 (ABCB6) in the regulation of melanogenesis in vitro.

Results

We found that ABCB6 inhibition could impair melanocyte maturation and melanin production in human melanoma (MNT-1) and immortalized human melanocyte (PIG1) cell lines. Moreover, ABCB6 knockdown inhibited the protein expression of melanocyte inducing microphthalmia-associated transcription factor (MITF) and its three downstream melanogenic enzymes (TYR, TYRP1 and TYRP2). Mechanistically, we revealed that ABCB6 could interact with and modulate glycogen synthase kinase 3 beta (GSK3-β) to exert its biological effect on melanogenesis.

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